调节性T细胞对输注树突状细胞后小鼠移植心脏的保护作用  

The protective effects of CD4^＋CD25^＋Treg cell on the allograft after infusion of dendritic cells with low expression of CD40 from donor in mouse heart transplantation

作　　者：朱杰昌[1] 付蔚华[1] 许翼麟[1] 朱理玮[1] 

机构地区：[1]天津医科大学总医院普通外科,300052

出　　处：《中华微生物学和免疫学杂志》2013年第4期298-302,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的探讨在输注供者低表达CD40的树突状细胞（dendriticcells，DC）后，调节性T细胞（regulatory T cell，Treg）对小鼠移植心脏的保护作用。方法以针对小鼠CD40基因的RNA干扰（RNAinterference，RNAi）慢病毒载体在体外感染供者骨髓来源的DC，制备低表达CD40的耐受性DC（T01-DC）。建立小鼠异位腹腔心脏移植模型。设置异系对照组、未感染DC组及单纯慢病毒感染DC组。观察各组移植心脏存活时间，评定术后7d移植物排斥反应、病理分级，并以流式细胞术检测手术前后外周血CD4^＋CD25^＋Treg变化水平。结果CD40-RNAi慢病毒载体在体外感染DC48h后，CIM0mRNA表达明显受到抑制，抑制效率为80．9％。CD40表达明显下降，由74．37％±4．08％降至40．07％±4．03％（P〈0．05）。与异系对照组和未感染DC组相比，单纯慢病毒感染DC组移植心脏存活时间（14±4）d明显延长（P〈0．01）；术后7d急性排斥反应病理分级均明显降低（P〈0．05）；术后3d．7d外周血CD4^＋CD25^＋Treg水平均明显升高（P〈0．05）。结论CD4^＋CD25^＋Treg对输注供者低表达CD40的树突状细胞的小鼠移植心脏具有保护作用。Objective To explore the effects of CD4^＋CD25^＋Treg cell on the allograft after infusion of dendritic ceils （DCs） with low expression of CIMO from donor in mouse heart transplantation. Methods In vitro, mouse bone marrow-derived DCs were infected by CD40-RNAi lentiviral vector, and toleregenic DCs （Tol-DCs） with low expression of CD40 were prepared. A heterotopic abdominal heart transplantation model was established in mice, and the other three groups that were control group, noninfected DC group and lentivirus infected DC group were designed correspondingly. Cardiac allograft survival time was recorded and pathological grading for acute rejection was assessed on the 7 d after heterotopie abdominal heart transplantation. Concentrations of CD4^＋CD25^＋Treg ceils in peripheral blood were analyzed before and after transplantation by flow eytometry. Results After 48 h infection of DCs by CD40-RNAi lentiviral vector in vitro, the expression of CD40 mRNA was down-regnlated significantly, whose inhibition rate was 80.9%. The expression of CD40 was decreased from 74.37% ±4.08% to 40.07% ± 4.03% （ P〈0.05 ） after 48 h infection. Compared with the control group and the noninfected DC group, the cardiac allograft survival time was significantly prolonged in the CD40-RNAi lentivirus infected DC group, which was （14 ± 4 ） d （P〈0.01） ; concentrations of CD4~CD25~Treg cells in peripheral blood were increasedboth on the 3 d and the 7 d after transplantation （ P〈0.05 ） ; the pathological grading for acute rejection was decreased on the 7 d after transplantation （P〈0.05）. Conclusion The CIM＋CD25＋Treg ceil in peripheral blood was protective to cardiac allograft in prolonging its survival time in mouse heart transplantation.

关 键 词：调节性T细胞 共刺激通路 树突状细胞 CD40 心脏移植 

分 类 号：R[医药卫生]